The specific aims of this proposal include the comparison of antigen handling by the lung and gut of inhalked and ingested antigen, and to dissect immunogenic and adjuvant requirements and mechanisms in the development of chronic hypersensitivity pneumonitis produced in the rabbit by repeated inhalation of antigen and muramyl dipeptide, a synthetic adjuvant. We plant to utilize fluorescein as a hapten in this system and to evaluate carrier (T-cell) requirements in immunogenesis and effector mechanisms; an amplified enzyme-linked immunosorbent assay (a-ELISA) will be utilized to measure specific antibodies of the various immunoglobulin classes. Localization of antigen, adjuvant and antibody-producing cells in lung, gut, spleen, and regional, central and peripheral lymph nodes will employ fluorenscence microscopy. Cellular interactions, antigen handling, the roles of immune complexes and antibody isotypes will thus be exploredin immunized and unimmunized animals and comparisons made between those developing chronic alveolitis and those undergoing desensitization. These studies should help clarify pathogenetic mechanisms causing lung injruy in an established rabbit model of hypersensitivity pneumonitis with implications for analogous human lung diseases, and will test a current hypothesis which postulates a common mucosal (secretory) immune system involving lung and gut and other nucosal surfaces.